Wine lactone, whose chemical name is (3a,4,5,7a)-tetrahydro-3,6-dimethyl-benzofuran-2(3H)-one, was found in 1975 by Southwell from metabolites in koalas. This compound was isolated from white wine in 1996 by Guth as being one of the most important aroma components of white wine and thus named as “wine lactone.” Wine lactone has eight types of stereoisomers, all of which were synthesized by Guth, and the compound naturally occurring (i.e., wine lactone) is a (3S,3aS,7aR) isomer. Among the eight types of stereoisomers, this (3S,3aS,7aR) isomer was found to have the strongest aroma and to be excellent in the quality of aroma (Non-patent Document 1: Helv. Chim. Acta, 79, (1996), 1559-1571).
There are various reports of how to produce wine lactone.
For example, Non-patent Document 1 (supra) reports a process for producing all stereoisomers including wine lactone, a process mediated by Diels-Alder reaction for 6-membered ring formation, and a process starting from limonene having the same stereochemistry as the 3a-position of wine lactone. However, the process for producing all stereoisomers is not cost-effective because wine lactone, i.e., the (3S,3aS,7aR) isomer which is excellent in aroma and the quality thereof is obtained in a yield as low as 20%. The process mediated by Diels-Alder reaction allows diastereoselective synthesis of a desired stereoisomer, but is not suitable for use on an industrial scale because of using harmful reagents, such as chromic acid for oxidation reaction and methyl iodide for methylation. The process starting from limonene is also difficult to use on an industrial scale because of using harmful reagents, such as chromic acid for oxidation reaction.
Non-patent Document 2 (J. Org. Chem., 46 (1981), 3896-3900) reports a process for obtaining wine lactone from a 2-cyclohexenol derivative through Claisen rearrangement reaction. According to this process, it is possible to synthesize wine lactone in a diastereoselective manner, but this process is not suitable for use on an industrial scale because of great difficulty in obtaining the starting 2-cyclohexenol derivative and because of using harmful reagents, such as methyl iodide for methylation.
Non-patent Document 3 (Eur. J. Org. Chem., (2000), 419-423) describes a process for obtaining wine lactone in a stereoselective manner through addition reaction of a malonic acid ester using a palladium complex as a catalyst. According to this process, it is possible to obtain only the (3S,3aS,7aR) isomer in a stereoselective manner. However, this process requires the stages of lactonization, lactone opening and recyclization, and hence involves a larger number of steps and complicated procedures. Moreover, this process is not suitable for use on an industrial scale because of using harmful reagents, such as methyl iodide for methylation.
Non-patent Document 4 (Tetrahedron: Asymmetry, 12, (2001), 2985-2988) discloses a process involving hydration of isolimonene and synthesis of a carboxylic acid through oxidation reaction, followed by ring closure reaction to synthesize wine lactone. According to this process, it is possible to synthesize a desired stereoisomer in a diastereoselective manner. However, this process is not suitable for use on an industrial scale because of using harmful reagents, such as chromic acid for oxidation reaction.
Patent Document 1 (JP 2004-269463 A) describes a process starting from a β-keto ester, which involves reduction of carbonyl groups using an optically active oxazaborolidine as an chiral ligand, followed by hydrolysis and cyclization reaction to synthesize wine lactone. However, this process also has a problem in using harmful reagents, such as butyl lithium and methyl iodide for methylation.
Patent Document 2 (JP 2010-195765 A) describes a process for obtaining wine lactone by simultaneous formation of two rings through Diels-Alder reaction. This process is advantageous in that wine lactone can be synthesized without using any harmful reagents, but it cannot be regarded as an industrially advantageous process because the temperature required for cyclization reaction is as very high as 200° C.